This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Background: Alcohol abuse and HIV infection are common and frequently coexist in the same individual. This project tests the hypothesis that alcohol functions as a cofactor to accelerate the progression of SIV infection, and to increase host susceptibility to opportunistic infections which will further accelerate disease progression. The purposes are to identify mechanisms by which alcohol impacts SIV disease progression by examining the host defense response to SIV, to study the effect of pneumonia on SIV expression, and to study the impact of alcohol on the efficacy and toxicity of antiretroviral therapy in SIV infected rhesus macaques. Methods: 24 rhesus macaques have had gastric catheters surgically implanted to administer either ethanol or sucrose (control subjects) for the duration of a protocol. Animals were infected with SIVmac251 3 months after starting alcohol and infected with Streptococcus pneumoniae 4 months after SIV inoculation. Some animals started to receive antiretroviral drugs at 2 months of SIV infection. Blood samples and bronchial alveolar lavage were obtained at selected times. Results/Discussion: Alcohol treatment increased plasmas viral set point. Analysis of SIV-specific CD4+ and CD8+ T cell response and anti-SIV antibody response failed to show an association between SIV-specific immune responses and viral load. In response to lung infection, SIV copies recovered in BAL fluid was increased in both sucrose and alcohol treated animals. The duration of the increase was greater in alcohol compared to sucrose animals (14 days vs 1 day). These studies indicate that alcohol abuse may accelerate disease progression, in part, by suppressing host defense against the infection and prolonging up regulation of virus production in response to an opportunistic infection. Studies have been initiated to examine the effect of alcohol on mucosal host defense, disease transmission, lung host defense, hematopoiesis, and muscle wasting in the presence and absence of muscle wasting.